Accepted_test

Tissue-specific and allele-specific activity of transcribed gene regulatory elements in human skeletal muscle
by Andrey Buyan | Vladimir Nozdrin | Guzel Gazizova | Georgy Meshcheryakov | Yoshihide Hayashizaki | Elena Shagimardanova | Oleg Gusev | Ivan Kulakovskiy | Institute of Protein Research, Russian Academy of Sciences, Pushchino, Russia; Research Laboratory «‎Regulatory Genomics», Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia | Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia | Research Laboratory «‎Regulatory Genomics», Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia | Institute of Protein Research, Russian Academy of Sciences, Pushchino, Russia | Research Laboratory «‎Regulatory Genomics», Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia | Research Laboratory «‎Regulatory Genomics», Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia; Life Improvement by Future Technologies (LIFT) Center, Moscow, Russia | Research Laboratory «‎Regulatory Genomics», Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia; Life Improvement by Future Technologies (LIFT) Center, Moscow, Russia | Institute of Protein Research, Russian Academy of Sciences, Pushchino, Russia; Research Laboratory «‎Regulatory Genomics», Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
Abstract ID: 163
Event: BGRS-abstracts
Sections: [Sym 1] Section “Regulatory genomics”

The rapid development of sequencing technologies over the last decades brought molecular genetics close to its medical applications. However, genome-based personalized medicine is still in its early age as its implementation requires reliable tools for annotating and interpreting individual genome variants, including widespread single-nucleotide variants (SNVs).

In this study, we utilized the cap analysis of gene expression (CAGE) data to construct an atlas of transcribed regulatory elements of diverse human skeletal muscles and assess the functional effect of SNVs by estimating the allelic imbalance in the transcriptional activity of promoters and enhancers.

As a result, we identified more than 20 thousand CAGE clusters, including more than 1.5 thousand bidirectional enhancers. More than 3/4 of promoters and enhancers exhibited tissue-specific activity across different skeletal muscles, highlighting very specific gene expression patterns in eye, tongue, and diaphragm. Next, we performed the SNV calling which yielded more than 15 thousand reliable variants and detected more than 6 thousand allele-specific events with a significant allelic imbalance in at least one skeletal muscle type.

We believe that our work will be useful for studying gene expression patterns and variant effects in healthy muscles as well as myopathies.